There is no known structural, functional, or genetic abnormality that singularly causes autism. Given that there is not a single cause of autism, it is advantageous to assess multiple biomarkers to better understand autism. This project builds upon our limited knowledge of the neurobiological basis of autism. In particular, this K01 proposal seeks to integrate structural and functional brain data to learn how structural defects cause neurological dysfunction, and how these structural and functional brain abnormalities gives rise to autism symptoms. A primary goal is to examine the auditory radiation and auditory cortex because functional and structural abnormalities of the auditory system are associated with autism. This project uses diffusion MRI to quantitatively assess the white matter of the auditory radiation and magnetoencephalogray (MEG) to measure activity within the superior temporal gyrus and determine neuronal timings of the auditory system. The first goal of this project is to develop HARDI metrics to assess the microstructure of specific white matter tracts. The second goal is to use HARDI fiber tracking along with the HARDI metrics to measure microstructural abnormalities in the auditory system associated with autism. The third is to correlate diffusion MR metrics with auditory cortex responses from MEG in children with autism. The fourth and final goal is to investigate the role of input from the frontal lobe on auditory corex activity. This unique suite of HARDI and MEG can provide converging evidence on the neurobiological basis of autism. This project is mentored by Dr. Timothy Roberts and Dr. Susan Levy. Training activities are planned to provide the candidate with expanded expertise in the experimental use of MEG and the clinical management of autism. The research and training program are designed to complement the candidate's background and lead to a career as an independent investigator of neuropsychiatric disorders. This proposal will be conducted within the laboratories and clinics of the Children's Hospital of Philadelphia (CHOP). The proposed K01 project takes advantage of unique resources and experts available at CHOP and the University of Pennsylvania. PUBLIC HEALTH RELEVANCE: Autism spectrum disorder (ASD) includes a variety of symptoms that disable children and result in lifelong impairment. Increased understanding of brain abnormalities in autism can lead to new diagnostic tools and earlier treatments. Improved treatment options can benefit public health by promoting the social development and integration of patients with autism.